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Biomedical subjects

M G Ervin

Publications and source records attributed to M G Ervin.

At least 91 records · Page 5Linked to original sources

Diurnal variations in plasma arginine vasotocin (AVT) concentrations in the ovine fetus.

Previously we have demonstrated the presence of AVT in the blood of fetal sheep. The source is not clear, but AVT has been identified in fetal pineal and pituitary glands. In view of the circadian secretory pattern of the pineal gland, we questioned whether fetal plasma AVT levels might vary diurnally. Plasma samples from five chronically catheterized ovine maternal ewes and fetal lambs 129-135 days' gestation were obtained at 3-19 hourly intervals for 1-2 days (mean +/- S.E.M. = 35 +/- 6 hours. Plasma AVT levels were determined by radioimmunoassay. Results were analyzed by nonlinear curve fitting procedures to relate hormone levels with time of day. Plasma AVT values for maternal ewes did not vary during the day in response to light/dark periods. The curve for mean fetal plasma AVT plotted against time showed oscillations with a period of about 25 hours (p less than 0.05). Peak fetal AVT levels were observed at 1600 hours and minimal levels at 0400 hours. These results indicate that ovine fetal AVT secretion varies diurnally. The site of AVT secretion may be the pineal gland; however, confirmation of this and identification of the physiological stimuli for secretion of fetal plasma AVT require further information.

Animals↗

Renal effects of ovine fetal arginine vasopressin secretion in response to maternal hyperosmolality.

Acute increases in maternal plasma osmolality can increase amniotic fluid osmolality. Amniotic fluid is primarily derived from fetal urine production, and arginine vasopressin infusion can affect both fetal urine production and amniotic fluid osmolality. To assess the effect of short-term changes in maternal osmolality on fetal arginine vasopressin secretion and renal function, six ewes of 126 +/- 1 days' gestation received intravenous infusions of 20% mannitol (500 ml/10 min). In response to mannitol infusion, both maternal and fetal plasma osmolality increased significantly (302 +/- 3 to 326 +/- 2 and 300 +/- 1 to 309 +/- 2 mosm, respectively). Increased fetal plasma and urine arginine vasopressin concentrations were associated with significant increases in fetal urine osmolality (146 +/- 12 to 262 +/- 30 mosm) and sodium concentration (35.8 +/- 2.8 to 76.5 +/- 20 mu Eq/ml), but fetal urine production rates did not change (0.68 +/- 0.11 to 0.62 +/- 0.15 ml/min). These conclusions were reached: Acute increases in maternal osmolality can affect fetal arginine vasopressin secretion; arginine vasopressin-induced increases in fetal urine osmolality may contribute to increased amniotic fluid osmolality in response to maternal hyperosmolality.

Amniotic Fluid↗

The plasma of pregnant women contains a novel oxytocin-vasotocin-like peptide.

Basal levels of immunoreactive oxytocin (OT) were measured in plasma of healthy pregnant women using two antisera to OT, Pitt Ab-1 and Pitt Ab-2, and an antiserum to arginine vasotocin, Tor AVT Ab. The mean (+/- SEM) level of immunoreactive OT Pitt Ab-1 was significantly higher, 7.7 +/- 0.9 microU/mL, than immunoreactive OT Pitt Ab-2, 0.9 +/- 0.2 microU/mL, P less than .001 measured in the same samples. AVT immunoreactivity in plasma of nonpregnant individuals was 0.8 +/- 0.16 pg/mL and in plasma of women in late pregnancy was 5.0 +/- 0.4 pg/mL. In four pregnant women receiving an infusion of synthetic OT (Pitocin, Parke-Davis, Morris Plains, NJ) a linear correlation was found between the dose of OT infused and the concentration of OT in plasma in samples measured with Pitt Ab-2, but no correlation was found in the same samples measured with Pitt Ab-1. Immunoreactive OT Pitt Ab-1 in plasma was not destroyed by a 60-minute incubation with pregnancy plasma. Pooled plasma from pregnant women was separated by reverse phase high pressure liquid chromatography (HPLC). OT Pitt Ab-1 and Tor AVT immunoreactivities in pregnancy plasma eluted in a position separate from synthetic OT. The differences found in levels of immunoreactive OT in the same samples of plasma measured with two antisera to OT illustrate an important reason why levels of OT in pregnant women may be reported to be variable among laboratories.

Chromatography, High Pressure Liquid↗

Breast stimulation contraction stress test: uterine contractions in the absence of oxytocin release.

The contraction stress test has been widely used to manage high-risk pregnancies. Breast-stimulated uterine contractions have been assumed to be mediated through oxytocin release. We studied 20 women undergoing a breast-stimulated contraction stress test. There was no significant increase in plasma oxytocin levels during this study in either test responders or nonresponders. These results suggest that the presence of a breast stimulation-uterine contraction reflex is not mediated by oxytocin.

Breast↗

Fetal recirculation of amniotic fluid arginine vasopressin.

Amniotic fluid volume reflects a balance between fetal lung fluid and fetal urine production and fluid reabsorption via fetal swallowing. Arginine vasopressin (AVP) infusion decreases both fetal lung fluid and urine production and increases amniotic fluid osmolality and AVP concentration. In the present study we assessed the effect of amniotic fluid AVP injection on plasma AVP (n = 6) and renal function (n = 4) in chronically catheterized fetal lambs (X gestation = 130 days). Thirty minutes after addition of 25 micrograms of synthetic AVP into the amniotic cavity, mean +/- SE fetal plasma AVP increased from a base line of 2.7 +/- 0.2 to 14.6 +/- 3.4 pg/ml (P less than 0.01). One hundred and twenty minutes after injection, plasma AVP had increased to 26.9 +/- 5.7 pg/ml. Fetal urine volume did not change (0.78 +/- 0.01 ml/min) but significant increases in urine osmolality (169 +/- 19 to 315 +/- 25 mosm) and urine sodium (64 +/- 11 to 125 +/- 11 mueq/ml) were observed 120 min after AVP administration. In conclusion, amniotic fluid AVP levels can affect fetal plasma AVP concentration, and AVP absorbed from the amniotic fluid by the fetus remains biologically active.

Amniotic Fluid↗

Isovolemic hypotension in ovine fetus: plasma arginine vasopressin response and urinary effects.

Chronically prepared third trimester fetal lambs were administered intravenous infusions of nitropruside. Mean basal systolic and diastolic blood pressure (59.8 and 42.4 mmHg, respectively) decreased significantly during the infusion (49.2 and 36.8 mmHg, respectively) and increased significantly during the recovery period (66.4 and 48.5 mmHg, respectively). Fetal plasma arginine vasopressin (AVP) significantly increased from a mean basal level of 1.25 +/- 0.09 to 6.81 +/- 0.39 pg/ml during the hypotensive period. Urinary AVP basal levels of 1.21 +/- 0.13 pg/ml increased to 3.18 +/- 0.66 pg/ml during the hypotensive period and 5.87 +/- 0.82 pg/ml during the recovery period (P less than 0.05). The fetal urinary response to nitroprusside appeared biphasic. The hypotensive phase was marked by decreases in both free water and osmolar clearances. During the recovery phase free water clearance remained decreased, while osmolar clearance returned to basal levels. Thus AVP secretion represents an important mechanism for ovine fetal modulation of solute and water excretion in response to utero hypotensive stress.

Animals↗

Continuous ovine fetal hemorrhage: sensitivity of plasma and urine arginine vasopressin response.

Intravascular hemorrhage of the ovine fetus is a potent stimulus for arginine vasopressin (AVP) secretion. However, the method (acute, continuous) and rate of blood withdrawal may influence the fetal response. To determine the hemorrhage threshold for AVP secretion in response to slow continuous hemorrhage, five chronically catheterized ovine fetuses were continuously hemorrhaged (0.6% blood vol/min) to 24-30% blood volume withdrawal. Immediately after hemorrhage fetal blood was reinfused at an equivalent rate. In addition to AVP measurements by radioimmunoassay, fetal urinary responses were monitored as an index of fetal AVP secretion. Significant increases in plasma AVP occurred during hemorrhage (1.0 +/- 0.1 to 8.0 +/- 2.0 pg/ml). The fetal plasma AVP-hemorrhage threshold, as defined by regression analysis, occurred at withdrawal of 13.0% blood volume. Fetal urine volume significantly decreased from a mean basal rate of 0.59 +/- 0.03 to 0.21 +/- 0.06 ml/min at the completion of hemorrhage. Urinary sodium, potassium, and osmolar excretion also significantly decreased at the completion of hemorrhage. Urinary AVP excretion, urine osmolality, sodium, and potassium concentrations did not change significantly during the hemorrhage period but increased significantly during the reinfusion period; the delay a result of renal and catheter dead space. Reinfusion of blood resulted in a return of plasma AVP to basal levels. These results define a threshold for AVP secretion and demonstrate significant urinary effects in response to slow continuous hemorrhage.

Animals↗

Changes in steady state plasma arginine vasotocin levels affect ovine fetal renal and cardiovascular function.

The neuropeptides arginine vasopressin (AVP) and arginine vasotocin (AVT) are present in ovine fetal plasma in similar concentrations. Although AVP appears to be an important factor in the regulation of fetal water metabolism, the significance of AVT in the fetus is not clear. In the present study we assessed the effects of changes in steady plasma AVT levels on renal and cardiovascular function of fetal lambs (mean gestation, 128 days) maintained with vascular and bladder catheters. Successive 1-h infusions of synthetic AVT (n = 8) at rates of 1.0 and 2.0 ng/min X kg resulted in steady state plasma AVT levels of 30 +/- 7 and 59 +/- 12 pg/ml, respectively. The AVT infusions increased both urinary AVT concentrations and urinary AVT excretion. Plasma and urinary AVT clearance rates (45 +/- 8.4 ml/min X kg and 0.38 +/- 0.13 ml/min, respectively) remained constant over the observed range of plasma AVT levels. Urinary AVT clearance accounted for less than 1% of the total plasma AVT clearance and was nonsaturable. Increases in plasma AVT augmented urinary osmolar excretion and osmolar clearance, and evoked a significant natriuresis. AVT at either 1 or 2 ng/min X kg decreased fetal heart rate and tended to increase blood pressure. These results suggest that AVT, like AVP, may be important in modulating ovine fetal electrolyte homeostasis.

Animals↗

Mirex-induced liver enlargement in rats is dependent upon an intact pituitary-adrenalcortical axis.

The effect of prior hypophysectomy upon mirex-induced liver hypertrophy in male Sprague-Dawley rats was examined. Mirex had no effect upon adrenal weight, liver weight, plasma glucose or plasma corticosterone in hypophysectomized rats. However, daily corticosterone supplements (20 mg/kg body weight, sc) given to mirex-treated hypophysectomized animals yielded a 52% increase in liver weight to body weight ratios over those observed in mirex-treated hypophysectomized animals not receiving supplement. In intact rats, both liver weight to body weight ratios and plasma ACTH were significantly increased over controls 2 days after mirex treatment. These results indicate that mirex-induced liver enlargement not only requires corticosterone, but that the response is dependent upon an intact pituitary-adrenalcortical axis.

Adrenal Cortex↗

Water excretion in preeclampsia: behavior as nephrotic syndrome.

Decreased free water excretion and the development of interstitial edema are recognized characteristics of preeclampsia. However, the pathophysiology of decreased urine excretion in preeclampsia is presently controversial: diminished glomerular filtration, renal arteriolar spasm, elevated plasma vasopressin levels, and plasma volume contraction have been suggested as etiologies. We studied seven pregnant patients with a diagnosis of mild preeclampsia to assess the role of vasopressin, serum protein, and glomerular function in the renal excretion of water. The ability to excrete a water load was significantly and directly correlated with serum albumin (P less than 0.05) and protein (P less than 0.02) concentrations. Neither plasma vasopressin nor creatinine clearance correlated with water excretion. The similarity of preeclampsia and the nephrotic syndrome with regard to the renal excretion of water is discussed.

Anuria↗

Amniotic fluid ionic concentration in response to chronic fetal vasopressin infusion.

Chronically prepared, third trimester fetal lambs were administered 72-h intravenous infusions of arginine vasopressin (AVP) (65 or 130 mU/kg h) or 0.9% saline. Saline infusion preceding the AVP infusion did not change amniotic fluid (AF) composition. During the AVP infusion, there were significant increases in amniotic fluid osmolality (278.8 +/- 4.9 to 302.1 +/- 4.5 mosm) and in sodium (122.7 +/- 3.3 to 135.3 +/- 3.6 meq/l) and potassium (9.7 +/- 2.6 to 13.8 +/- 1.3 meq/l) concentrations. Saline infusion after the AVP infusion resulted in return of AF osmolality, sodium, and potassium toward normal levels. Fetal plasma and amniotic fluid AVP levels measured by radioimmunoassay significantly increased during AVP infusion and decreased during the subsequent saline infusion. There were no changes in maternal or fetal plasma osmolality in response to AVP. These results suggest that fetal AVP released in response to intrauterine stress may alter the composition and osmolality of amniotic fluid in a reversible manner.

Amniotic Fluid↗

Arginine vasotocin in ovine fetal blood, urine, and amniotic fluid.

Arginine vasotocin ([8-arginine]-oxytocin) (AVT), the primary antidiuretic principle in submammalian vertebrates, has been reported to be present in mammalian pituitary and pineal glands. Although the most phyletically ubiquitous of the known neurohypophysial peptides, AVT is still not recognized as a mammalian hormone. We examined plasma, urine, and amniotic fluid from fetal lambs by radioimmunoassay (RIA) for evidence of AVT to assess the possibility of its being such a hormone. Measureable quantities of AVT-like immunoreactivity (irAVT) were observed in fetal plasma (2.4 +/- 0.2 pg/ml), urine (1.4 +/- 0.2 pg/ml), and amniotic fluid (1.9 +/- 0.2 pg/ml). Since the AVT antiserum shows minimal cross-reactivity with arginine vasopressin (AVP) and oxytocin (OT), measurements of AVP and OT concentrations in the same biological fluids also were conducted with specific antisera. The results suggest that the irAVT was not accountable on the basis of cross-reaction. To further verify the identity of the irAVT, a high pressure liquid chromatography system using RIA as a means of detection was developed. This system is sufficiently sensitive to allow the separation and quantitation of picogram quantities of the synthetic peptides AVT, AVP, and OT. In this system, the irAVT in fetal plasma, urine, and amniotic fluid appeared as a single peak coeluting with synthetic AVT. These results indicate that AVT is present in ovine fetal plasma and support the view that the fetus secretes this peptide. The physiological significance of circulating AVT remains to be defined.

Amniotic Fluid↗

Ovine fetal-maternal water transfer is independent of fetal prolactin levels.

To examine the effect of prolactin (PRL) on transplacental water flow, we infused mannitol (500 ml; 20% solution) over 10 min into five chronically catheterized ewes (121-134 days' gestation), producing a peak maternal plasma osmolality by 10 min and fetal osmolality by 20 min. One day before or after, an identical amount of mannitol was infused into the same ewe during the 2nd h of a 2-h infusion of PRL (40 +/- 2.2 micrograms/h) into a fetal leg vein. Mean (+/- SE) fetal plasma PRL levels were 6.9 +/- 3.2 ng/ml at baseline. Steady state fetal PRL levels were 17.7 +/- 7.4 ng/ml during PRL infusion. Maternal mannitol infused without administration of PRL to the fetus evoked a rise in fetal plasma osmolality similar to that following maternal mannitol during PRL administration to the fetus. Thus, as shown previously, PRL affects water permeability across the membranous chorioamnion, whereas results of the present study indicate that the hormone does not affect water transfer across the ovine chorionic villi (placenta).

Animals↗

A novel oxytocin-like and vasotocin-like peptide in human plasma after administration of estrogen.

Using three antisera to oxytocin (OT Pitt Ab-1, OT Pitt Ab-2, and TOR OT Ab), we found comparable levels of OT in response to infant suckling and during infusion of synthetic OT, and identical standard curves with biological and synthetic standards of OT. Pitt Ab-1, but not Pitt Ab-2 or TOR OT Ab, measured increased OT in response to estrogen. Using an arginine vasotocin RIA (TOR AVT Ab), we found an increase in AVT immunoreactivity after estrogen treatment. Mean basal OT levels measured with OT Pitt Ab-2 in plasma of men [0.75 +/- 0.06 (+/- SEM) microU/ml] and women (0.8 +/- 0.09 microU/ml) were lower than OT measured with Pitt Ab-1 (1.7 +/- 0.09 microU/ml in men and 1.7 +/- 0.07 microU/al in women; P less than 0.001). Mean OT measured with Pitt Ab-2 in the plasma of women given estrogen chronically (0.8 +/- 0.04 microU/ml) and acutely (0.6 +/- 0.15 microU/ml) were not significantly different from basal levels. OT levels measured with Pitt Ab-1 in the same samples were 4.6 +/- 0.5 and 4.3 +/- 0.5 microU/ml, respectively, both significantly increased from basal levels (P less than 0.001) and significantly higher than OT measured with Pitt Ab-2 (P less than 0.001). Mean OT measured with Pitt Ab-1 in the plasma of pregnant women was 8.6 +/- 1.02 microU/ml, significantly higher than OT measured with Pitt Ab-2 (1.0 +/- 0.3 microU/ml; P less than 0.001). Men given 25 mg diethylstilbestrol had significant increases in OT measured with Pitt Ab-1 and in AVT measured with TOR AVT (P less than 0.01), but not in OT measured with Pitt Ab-2. Plasma from a man given diethylstilbestrol was prepared for high performance liquid chromatography and applied to a C18 muBondapak reverse phase column. The plasma contained two peaks of immunoreactivity detected as OT with Pitt Ab-1 and as AVT using TOR AVT Ab. The material was not detected by Pitt Ab-2 or TOR OT Ab and did not coelute with standards of OT, AVT, or AVP. Pregnancy plasma, thioglycolic acid, chymotrypsin, and trypsin reduced Pitt Ab-1, Pitt Ab-2, and TOR OT immunoreactivity of synthetic OT. The percent recovery of OT immunoreactivity was not significantly different with Pitt Ab-1 vs. Pitt Ab-2. A novel peptide, which is increased in response to administered estrogen, is present in human plasma and is detected by some antisera to OT and AVT. The observation explains the wide variability in OT levels in the estrogen-primed state and provides a new mechanism to study estrogen-related physiology and pathophysiology.

Adult↗

High pressure liquid chromatographic separation of an oxytocin/arginine vasotocin-like peptide from the plasma of patients with chronic renal failure.

Levels of a novel oxytocin (OT)- and arginine vasotocin (AVT)-like peptide detected by one antiserum to OT (Pitt Ab-1) and one antiserum to AVT (Tor AVT) were recently found to rise in human plasma in response to administration of estrogen. The novel peptide rose in parallel with the estrogen-stimulated neurophysin (ESN). The mean level (+/- SEM) of ESN in plasma of 11 individuals with altered renal function (nondialyzed) was significantly higher than the level in individuals with normal renal function (4.2 +/- 0.9 vs. 1.1 +/- 0.04 ng/ml; P less than 0.01). In patients treated with hemo- or peritoneal dialysis, mean (+/- SEM) levels of ESN were 18.1 +/- 3.2 and 16.8 +/- 3.7 ng/ml, respectively. Levels of estradiol and estrone were not elevated and did not correlate with high levels of ESN. Levels of OT Pitt Ab-1, AVT, and ESN immunoreactivity were measured in plasma form nine patients undergoing hemodialysis and eight patients undergoing peritoneal dialysis. Mean (+/- SEM) levels of all three peptides were elevated (12.9 +/- 1.5 microU/ml, 32.1 +/- 6.7 pg/ml, and 13.5 +/- 4.0 ng/ml, respectively). ESN was significantly correlated with OT Pitt Ab-1 and AVT (R2 = 0.80; P less than 0.001). Plasma samples from the same patients were pooled, treated, and separated by reverse phase HPLC. The plasma contained a peak of immunoreactivity detected by Pitt Ab-1 and Tor AVT Ab. The position of the material was distinct from that of synthetic OT, AVT, or AVP and corresponded to the position of the novel OT-like peptide found in plasma of individuals given estrogen. The findings support parallel secretion of the OT-like peptide with ESN and represent the first disease state characterized by high levels of this OT- and AVT-like peptide.

Adult↗

Bulk flow of amniotic fluid water in response to maternal osmotic challenge.

Amniotic fluid volume is regulated by a complex system of fluid exchanges with fetal and maternal fluid compartments. To assess possible hormonal control of amniotic fluid water exchange with the maternal vascular compartment, we studied the effect of intra-amniotic injections of prolactin, vasopressin, or vasotocin on the amniotic to maternal water flux induced by the acute intravenous infusion of mannitol to the pregnant ewe. This mannitol stimulus increased amniotic fluid osmolality secondary to a shift of free water to the maternal vascular/extracellular compartments. Prior intra-amniotic injection of prolactin but not vasopressin or vasotocin blunted the amniotic fluid osmolar response to maternal mannitol infusion. These results suggest that resorption of amniotic fluid water may occur at the chorioamnion and that amniotic fluid prolactin may have a regulatory function in amniotic fluid volume and osmolar homeostasis.

Amniotic Fluid↗

Fetal lung fluid response to maternal hyperosmolality.

Lung fluid production in utero, a significant source of amniotic fluid, may be regulated by the fetus in response to environmental stress. We monitored changes of maternal and fetal plasma osmolality, plasma arginine vasopressin level, and fetal lung fluid production in response to mannitol-induced change in maternal osmolality in five chronically catheterized ovine fetuses. Four additional ewes and their fetuses did not receive mannitol and served as controls. Maternal infusion of 20% mannitol resulted in maternal and subsequent fetal hyperosmolality (changing from 303 +/- 2 to 322 +/- 2 mOsm and 300 +/- 5 to 319 +/- 8 mOsm, respectively), Mean fetal lung fluid production significantly decreased (from 2.6 +/- 0.4 to 1.6 +/- 0.4 ml/10 min), whereas lung fluid osmolality significantly increased (from 298 +/- 2 to 303 +/- 3 mOsm) in the study animals. No changes in lung fluid sodium or potassium concentrations were observed in study or control fetuses. Fetal plasma arginine vasopressin level significantly increased in the study fetuses (2.2 +/- 0.3 to 5.3 +/- 1.6 microU/ml), though not in control animals. These results indicate that the fetal lamb responds to increased osmolality by decreasing lung fluid production, and that there is a concomitant increase in lung fluid osmolality. This response appears to be mediated via increased fetal plasma vasopressin levels.

Animals↗